The major myosin-binding domain of skeletal muscle MyBP-C (C protein) resides in the COOH-terminal, immunoglobulin C2 motif.

A common feature shared by myosin-binding proteins from a wide variety of species is the presence of a variable number of related internal motifs homologous to either the Ig C2 or the fibronectin (Fn) type III repeats. Despite interest in the potential function of these motifs, no group has clearly demonstrated a function for these sequences in muscle, either intra- or extracellularly. We have completed the nucleotide sequence of the fast type isoform of MyBP-C (C protein) from chicken skeletal muscle. The deduced amino acid sequence reveals seven Ig C2 sets and three Fn type III motifs in MyBP-C. alpha-chymotryptic digestion of purified MyBP-C gives rise to four peptides. NH2-terminal sequencing of these peptides allowed us to map the position of each along the primary structure of the protein. The 28-kD peptide contains the NH2-terminal sequence of MyBP-C, including the first C2 repeat. It is followed by two internal peptides, one of 5 kD containing exclusively spacer sequences between the first and second C2 motifs, and a 95-kD fragment containing five C2 domains and three fibronectin type III motifs. The C-terminal sequence of MyBP-C is present in a 14-kD peptide which contains only the last C2 repeat. We examined the binding properties of these fragments to reconstituted (synthetic) myosin filaments. Only the COOH-terminal 14-kD peptide is capable of binding myosin with high affinity. The NH2-terminal 28-kD fragment has no myosin-binding, while the long internal 100-kD peptide shows very weak binding to myosin. We have expressed and purified the 14-kD peptide in Escherichia coli. The recombinant protein exhibits saturable binding to myosin with an affinity comparable to that of the 14-kD fragment obtained by proteolytic digestion (1/2 max binding at approximately 0.5 microM). These results indicate that the binding to myosin filaments is mainly restricted to the last 102 amino acids of MyBP-C. The remainder of the molecule (1,032 amino acids) could interact with titin, MyBP-H (H protein) or thin filament components. A comparison of the highly conserved Ig C2 domains present at the COOH-terminus of five MyBPs thus far sequenced (human slow and fast MyBP-C, human and chicken MyBP-H, and chicken MyBP-C) was used to identify residues unique to these myosin-binding Ig C2 repeats

Hypoxia, fetal and neonatal physiology: 100 years on from Sir Joseph Barcroft.

This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27200

Do stellar magnetic cycles influence the measurement of precise radial velocities?

The ever increasing level of precision achieved by present and future radial-velocity instruments is opening the way to discovering very low-mass, long-period planets (e.g. solar-system analogs). These systems will be detectable as low-amplitude signals in radial-velocity (RV). However, an important obstacle to their detection may be the existence of stellar magnetic cycles on similar timescales. Here we present the results of a long-term program to simultaneously measure radial-velocities and stellar-activity indicators (CaII, H_alpha, HeI) for a sample of stars with known activity cycles. Our results suggest that all these stellar activity indexes can be used to trace the stellar magnetic cycle in solar-type stars. Likewise, we find clear indications that different parameters of the HARPS cross-correlation function (BIS, FWHM, and contrast) are also sensitive to activity level variations. Finally, we show that, although in a few cases slight correlations or anti-correlations between radial-velocity and the activity level of the star exist, their origin is still not clear. We can, however, conclude that for our targets (early-K dwarfs) we do not find evidence of any radial-velocity variations induced by variations of the stellar magnetic cycle with amplitudes significantly above ~1 m/s.Comment: Accepted for publication in A&A (revised version following minor language corrections

Quantifying Rapid Variability in Accreting Compact Objects

I discuss some practical aspects of the analysis of millisecond time variability X-ray data obtained from accreting neutron stars and black holes. First I give an account of the statistical methods that are at present commonly applied in this field. These are mostly based on Fourier techniques. To a large extent these methods work well: they give astronomers the answers they need. Then I discuss a number of statistical questions that astronomers don't really know how to solve properly and that statisticians may have ideas about. These questions have to do with the highest and the lowest frequency ranges accessible in the Fourier analysis: how do you determine the shortest time scale present in the variability, how do you measure steep low-frequency noise. The point is stressed that in order for any method that resolves these issues to become popular, it is necessary to retain the capabilities the current methods already have in quantifying the complex, concurrent variability processes characteristic of accreting neutron stars and black holes.Comment: To be published in the Proceedings of "Statistical Challenges in Modern Astronomy II", University Park PA, USA, June 199

Beryllium anomalies in solar-type field stars

We present a study of beryllium (Be) abundances in a large sample of field solar-type dwarfs and sub-giants spanning a large range of effective temperatures. The analysis shows that Be is severely depleted for F stars, as expected by the light-element depletion models. However, we also show that Beryllium abundances decrease with decreasing temperature for stars cooler than $\sim$6000 K, a result that cannot be explained by current theoretical models including rotational mixing, but that is, at least in part, expected from the models that take into account internal wave physics. In particular, the light element abundances of the coolest and youngest stars in our sample suggest that Be, as well as lithium (Li), has already been burned early during their evolution. Furthermore, we find strong evidence for the existence of a Be-gap for solar-temperature stars. The analysis of Li and Be abundances in the sub-giants of our sample also shows the presence of one case that has still detectable amounts of Li, while Be is severely depleted. Finally, we compare the derived Be abundances with Li abundances derived using the same set of stellar parameters. This gives us the possibility to explore the temperatures for which the onset of Li and Be depletion occurs.Comment: 16 pages, 13 figures, accepted for publication in Astronomy & Astrophysic

Investigating white matter fibre density and morphology using fixel-based analysis

Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order diffusion models, parameters related to fibre density can be extracted for individual fibre populations within each voxel (‘fixels’), and recent advances in statistics enable the multi-subject analysis of such data. However, investigating within-voxel microscopic fibre density alone does not account for macroscopic differences in the white matter morphology (e.g. the calibre of a fibre bundle). In this work, we introduce a novel method to investigate the latter, which we call fixel-based morphometry (FBM). To obtain a more complete measure related to the total number of white matter axons, information from both within-voxel microscopic fibre density and macroscopic morphology must be combined. We therefore present the FBM method as an integral piece within a comprehensive fixel-based analysis framework to investigate measures of fibre density, fibre-bundle morphology (cross-section), and a combined measure of fibre density and cross-section. We performed simulations to demonstrate the proposed measures using various transformations of a numerical fibre bundle phantom. Finally, we provide an example of such an analysis by comparing a clinical patient group to a healthy control group, which demonstrates that all three measures provide distinct and complementary information. By capturing information from both sources, the combined fibre density and cross-section measure is likely to be more sensitive to certain pathologies and more directly interpretable

Bisectors of the HARPS Cross-Correlation-Function. The dependence on stellar atmospheric parameters

Bisectors of the HARPS cross-correlation function (CCF) can discern between planetary radial-velocity (RV) signals and spurious RV signals from stellar magnetic activity variations. However, little is known about the effects of the stellar atmosphere on CCF bisectors or how these effects vary with spectral type and luminosity class. Here we investigate the variations in the shapes of HARPS CCF bisectors across the HR diagram in order to relate these to the basic stellar parameters, surface gravity and temperature. We use archive spectra of 67 well studied stars observed with HARPS and extract mean CCF bisectors. We derive previously defined bisector measures (BIS, v_bot, c_b) and we define and derive a new measure called the CCF Bisector Span (CBS) from the minimum radius of curvature on direct fits to the CCF bisector. We show that the bisector measures correlate differently, and non-linearly with log g and T_eff. The resulting correlations allow for the estimation of log g and T_eff from the bisector measures. We compare our results with 3D stellar atmosphere models and show that we can reproduce the shape of the CCF bisector for the Sun.Comment: 13 pages, 20 figures. Accepted by A&

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Planets around evolved intermediate-mass stars. I. Two substellar companions in the open clusters NGC 2423 and NGC 4349

Context. Many efforts are being made to characterize extrasolar planetary systems and unveil the fundamental mechanisms of planet formation. An important aspect of the problem, which remains largely unknown, is to understand how the planet formation process depends on the mass of the parent star. In particular, as most planets discovered to date orbit a solar-mass primary, little is known about planet formation around more massive stars. Aims. To investigate this point, we present first results from a radial velocity planet search around red giants in the clump of intermediate-age open clusters. We choose clusters harbouring red giants with masses between 1.5 and 4 M_sun, using the well-known cluster parameters to accurately determine the stellar masses. We are therefore exploring a poorly-known domain of primary masses, which will bring new insights into the properties of extrasolar planetary systems. Methods. We are following a sample of about 115 red giants with the Coralie and HARPS spectrographs to obtain high-precision radial velocity (RV) measurements and detect giant planets around these stars. We use bisector and activity index diagnostics to distinguish between planetary-induced RV variations and stellar photospheric jitter. Results. We present the discoveries of a giant planet and a brown dwarf in the open clusters NGC 2423 and NGC 4349, orbiting the 2.4 M_sun-star NGC2423 No3 (TYC 5409-2156-1) and the 3.9 M_sun-star NGC4349 No127 (TYC 8975-2606-1). These low-mass companions have orbital periods of 714 and 678 days and minimum masses of 10.6 and 19.8 M_jup, respectively. Combined with the other known planetary systems, these detections indicate that the frequency of massive planets is higher around intermediate-mass stars, and therefore probably scales with the mass of the protoplanetary disk.Comment: 9 pages, 11 figures, accepted for publication in A&

Towards an Ontology-Based Approach for Reusing Non-Functional Requirements Knowledge

Requirements Engineering play a crucial role during the software development process. Many works have pointed out that Non-Functional Requirements (NFR) are currently more important than Functional Requirements. NFRs can be very complicated to understand due to its diversity and subjective nature. The NDR Framework has been proposed to fill some of the existing gaps to facilitate NFR elicitation and modeling. In this thesis, we introduce a tool that plays a major role in the NDR Framework allowing software engineers to store and reuse NFR knowledge. The NDR Tool converts the knowledge contained in Softgoal Interdependency Graphs (SIGs) into a machine-readable format that follows the NFR and Design Rationale (NDR) Ontology. It also provides mechanisms to query the knowledge base and produces graphical representation for the results obtained. To evaluate whether our approach aids eliciting NFRs, we conducted an experiment performing a software development scenario